Lysinyl macrocyclic hexaoxazoles: synthesis and selective G-quadruplex stabilizing properties

Bioorg Med Chem Lett. 2008 Feb 1;18(3):913-7. doi: 10.1016/j.bmcl.2007.12.048. Epub 2008 Jan 14.

Abstract

Macrocyclic hexaoxazoles having one or two lysinyl side chains in which the terminal nitrogen is either a primary amine, N,N-dimethylamine, or an acetamide have been synthesized. Sodium ion has been found to be beneficial to the macrocyclization step by acting as a template around which the linear polyoxazole can organize. Each of the targeted compounds selectivity stabilizes G-quadruplex versus duplex DNA. Compounds with one valine and one lysine residue display the best combination of G-quadruplex stabilizing ability with no detectable stabilization of duplex DNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA / drug effects*
  • Drug Design
  • G-Quadruplexes*
  • Lysine / chemistry*
  • Lysine / pharmacology*
  • Macrocyclic Compounds / chemical synthesis*
  • Macrocyclic Compounds / chemistry
  • Macrocyclic Compounds / pharmacology*
  • Molecular Structure
  • Oxazoles / chemical synthesis*
  • Oxazoles / chemistry
  • Oxazoles / pharmacology*
  • Structure-Activity Relationship

Substances

  • Macrocyclic Compounds
  • Oxazoles
  • DNA
  • Lysine